Mindfulness in the focus of the neurosciences - The contribution of neuroimaging to the understanding of mindfulness.

Background: Mindfulness affects human levels of experience by facilitating the immediate and impartial perception of phenomena, including sensory stimulation, emotions, and thoughts. Mindfulness is now a focus of neuroimaging, since technical and methodological developments in magnetic resonance imaging have made it possible to observe subjects performing mindfulness tasks. Objective: We set out to describe the association between mental processes and characteristics of mindfulness, including their specific cerebral patterns, as shown in structural and functional neuroimaging studies. Methods: We searched the MEDLINE databank of references and abstracts on life sciences and biomedical topics via PubMed using the keywords: "mindfulness," "focused attention (FA)," "open monitoring (OM)," "mind wandering," "emotional regulation," "magnetic resonance imaging (MRI)" and "default mode network (DMN)." This review extracted phenomenological experiences across populations with varying degrees of mindfulness training and correlated these experiences with structural and functional neuroimaging patterns. Our goal was to describe how mindful behavior was processed by the constituents of the default mode network during specific tasks. Results and conclusions: Depending on the research paradigm employed to explore mindfulness, investigations of function that used fMRI exhibited distinct activation patterns and functional connectivities. Basic to mindfulness is a long-term process of learning to use meditation techniques. Meditators progress from voluntary control of emotions and subjective preferences to emotional regulation and impartial awareness of phenomena. As their ability to monitor perception and behavior, a metacognitive skill, improves, mindfulness increases self-specifying thoughts governed by the experiential phenomenological self and reduces self-relational thoughts of the narrative self. The degree of mindfulness (ratio of self-specifying to self-relational thoughts) may affect other mental processes, e.g., awareness, working memory, mind wandering and belief formation. Mindfulness prevents habituation and the constant assumptions associated with mindlessness. Self-specifying thinking during mindfulness and self-relational thinking in the narrative self relies on the default mode network. The main constituents of this network are the dorsal and medial prefrontal cortex, and posterior cingulate cortex. These midline structures are antagonistic to self-specifying and self-relational processes, since the predominant process determines their differential involvement. Functional and brain volume changes indicate brain plasticity, mediated by mental training over the long-term.

Distinguishing transient from persistent tactile agnosia after partial anterior circulation infarcts - Behavioral and neuroimaging evidence for white matter disconnection.

From a cohort of 36 patients presenting apperceptive tactile agnosia after first cortical ischemic stroke, 14 showed temporary impairment at admission. A previous multi-voxel analysis of the cortical lesions, using as explanatory variable the course of tactile object recognition performance over the recovery period of 9 months, partitioned the cohort into three subgroups. Of the 14 patients constituting two of the subgroups, 7 recovered from their impairment whereas 7 did not. These two subgroups could not be distinguished at admission. The primary aim of the present study is to present two assessments that can do so. The first assessment comprises a pattern of behavioral measures, determined via principal component analysis, encoded in three tests: picking small objects, macrogeometrical discrimination and tactile object recognition. The receiver operating characteristic curve derived from permutation of the behavioral test scores yielded an 80% probability of correct identification of the patient subgroup and an 8% probability for false identification. As done with the permuted scores, the pattern could predict the persistence of affliction of new stroke patients with tactile agnosia. The second predictive assessment extends our previous evaluation of cortical MRI lesion maps to include subcortical regions. Confirming our previous study, the lesions of the persistently impaired subgroup disrupted significantly the anterior arcuatus fasciculus and associated superior longitudinal fasciculus III in the ipsilesional hemisphere, impeding reciprocal information transfer between supramarginal gyrus and both the ventral premotor cortex and Brodmann area 44. Due to the importance of interhemispheric information transfer in tactile agnosia, we performed a supplementary analysis of tactile object recognition scores. It showed that haptic information transfer from the non-affected to the affected hands in the persistent cases partly restored function during the nine months, possibly following restoration of functional interhemispheric haptic information transfer at the border of posterior corpus callosum and splenium. In conclusion, the combined findings of the cortical lesion at subarea PFt of the inferior parietal lobule and the associated subcortical tract lesions permit almost perfect prediction of persistent impairment of tactile object recognition. The study substantiates the need for combined analysis of both cortical lesions and white matter tract disconnections.

Sensing form - finger gaiting as key to tactile object exploration - a data glove analysis of a prototypical daily task.

BACKGROUND: Motor hand skill and associated dexterity is important for meeting the challenges of daily activity and an important resource post-stroke. In this context, the present study investigated the finger movements of right-handed subjects during tactile manipulation of a cuboid, a prototypical task underlying tactile exploration. During one motor act, the thumb and fingers of one hand surround the cuboid in a continuous and regular manner. While the object is moved by the guiding thumb, the opposed supporting fingers are replaced once they reach their joint limits by free fingers, a mechanism termed finger gaiting. METHODS: For both hands of 22 subjects, we acquired the time series of consecutive manipulations of a cuboid at a frequency of 1 Hz, using a digital data glove consisting of 29 sensors. Using principle component analysis, we decomposed the short action into motor patterns related to successive manipulations of the cuboid. The components purport to represent changing grasp configurations involving the stabilizing fingers and guiding thumb. The temporal features of the components permits testing whether the distinct configurations occur at the frequency of 1 Hz, i.e. within the time window of 1 s, and, thus, taxonomic classification of the manipulation as finger gaiting. RESULTS: The fraction of variance described by the principal components indicated that three components described the salient features of the single motor acts for each hand. Striking in the finger patterns was the prominent and varying roles of the MCP and PIP joints of the fingers, and the CMC joint of the thumb. An important aspect of the three components was their representation of distinct finger configurations within the same motor act. Principal component and graph theory analysis confirmed modular, functionally synchronous action of the involved joints. The computation of finger trajectories in one subject illustrated the workspace of the task, which differed for the right and left hands. CONCLUSION: In this task one complex motor act of 1 s duration could be described by three elementary and hierarchically ordered grasp configurations occurring at the prescribed frequency of 1 Hz. Therefore, these configurations represent finger gaiting, described until now only in artificial systems, as the principal mechanism underlying this prototypical task. TRIAL REGISTRATION: clinicaltrials.gov, NCT02865642 , registered 12 August 2016.

Early prediction of long-term tactile object recognition performance after sensorimotor stroke.

Until now tactile agnosia has been reported only in small, but detailed cross-sectional case studies. Here we show that multi-voxel pattern analysis (MVPA) of early diffusion-weighted lesion maps can be used to accurately predict long-term recovery of tactile object recognition (TOR) in 35 subjects with varying hand skill impairment and associated specific daily activity limitation after cortical sensori-motor stroke. Multiple regression analysis revealed the essentially dysfunctional subprocesses for object recognition in the specifically impaired subjects, i.e., grasping as determined by a subtest of Jebsen Taylor hand function test, and perception of macrogeometrical object properties. The Gaussian process regression of MVPA represents a function that relates a selection of lesioned voxels as input variables to TOR performance scores as target variables. On the behavioural level, patients fell into three recovery subgroups, depending on TOR performance over the observation period. Only baseline motor hand skill and shape discrimination were significantly correlated with the TOR trajectories. To define functionally meaningful voxels, we combined information from MVPA of lesion maps and a priori knowledge of regions of interest derived from a data bank for shape recognition. A high significance for the predicted TOR performances over nine months could be verified by permutation tests, leading us to expect that the model generalises to larger patient cohorts with first cortical ischemic stroke. The lesion sites of the persistently impaired subjects exhibited an overlap with critical areas related to the MVPA prediction map in the cytoarchitectonic areas PFt of inferior parietal lobule and OP1 of parietal operculum which are associated with higher order sensory processing. This ultimate check corroborated the significance of the MVPA map for the prediction of tactile object recognition. The clinical implication of our study is that neuroimaging data acquired immediately after first stroke could facilitate individual forecasting of post-stroke recovery.

Development and Validation of a Prognostic Model of Swallowing Recovery and Enteral Tube Feeding After Ischemic Stroke.

Importance: Predicting the duration of poststroke dysphagia is important to guide therapeutic decisions. Guidelines recommend nasogastric tube (NGT) feeding if swallowing impairment persists for 7 days or longer and percutaneous endoscopic gastrostomy (PEG) placement if dysphagia does not recover within 30 days, but, to our knowledge, a systematic prediction method does not exist. Objective: To develop and validate a prognostic model predicting swallowing recovery and the need for enteral tube feeding. Design, Setting, and Participants: We enrolled participants with consecutive admissions for acute ischemic stroke and initially severe dysphagia in a prospective single-center derivation (2011-2014) and a multicenter validation (July 2015-March 2018) cohort study in 5 tertiary stroke referral centers in Switzerland. Exposures: Severely impaired oral intake at admission (Functional Oral Intake Scale score <5). Main Outcomes and Measures: Recovery of oral intake (primary end point, Functional Oral Intake Scale ≥5) or return to prestroke diet (secondary end point) measured 7 (indication for NGT feeding) and 30 (indication for PEG feeding) days after stroke. Results: In total, 279 participants (131 women [47.0%]; median age, 77 years [interquartile range, 67-84 years]) were enrolled (153 [54.8%] in the derivation study; 126 [45.2%] in the validation cohort). Overall, 64% (95% CI, 59-71) participants failed to recover functional oral intake within 7 days and 30% (95% CI, 24-37) within 30 days. Prolonged swallowing recovery was independently associated with poor outcomes after stroke. The final prognostic model, the Predictive Swallowing Score, included 5 variables: age, stroke severity on admission, lesion location, initial risk of aspiration, and initial impairment of oral intake. Predictive Swallowing Score prediction estimates ranged from 5% (score, 0) to 96% (score, 10) for a persistent impairment of oral intake on day 7 and from 2% to 62% on day 30. Model performance in the validation cohort showed a discrimination (C statistic) of 0.84 (95% CI, 0.76-0.91; P < .001) for predicting the recovery of oral intake on day 7 and 0.77 (95% CI, 0.67-0.87; P < .001) on day 30, and a discrimination for a return to prestroke diet of 0.94 (day 7; 95% CI, 0.87-1.00; P < .001) and 0.71 (day 30; 95% CI, 0.61-0.82; P < .001). Calibration plots showed high agreement between the predicted and observed outcomes. Conclusions and Relevance: The Predictive Swallowing Score, available as a smartphone application, is an easily applied prognostic instrument that reliably predicts swallowing recovery. It will support decision making for NGT or PEG insertion after ischemic stroke and is a step toward personalized medicine.

Relating Acute Lesion Loads to Chronic Outcome in Ischemic Stroke-An Exploratory Comparison of Mismatch Patterns and Predictive Modeling.

Objectives: To investigate the relationship between imaging features derived from lesion loads and 3 month clinical assessments in ischemic stroke patients. To support clinically implementable predictive modeling with information from lesion-load features. Methods: A retrospective cohort of ischemic stroke patients was studied. The dataset was dichotomized based on revascularization treatment outcome (TICI score). Three lesion delineations were derived from magnetic resonance imaging in each group: two clinically implementable (threshold based and fully automatic prediction) and 90-day follow-up as final groundtruth. Lesion load imaging features were created through overlay of the lesion delineations on a histological brain atlas, and were correlated with the clinical assessment (NIHSS). Significance of the correlations was assessed by constructing confidence intervals using bootstrap sampling. Results: Overall, high correlations between lesion loads and clinical score were observed (up to 0.859). Delineations derived from acute imaging yielded on average somewhat lower correlations than delineations derived from 90-day follow-up imaging. Correlations suggest that both total lesion volume and corticospinal tract lesion load are associated with functional outcome, and in addition highlight other potential areas associated with poor clinical outcome, including the primary somatosensory cortex BA3a. Fully automatic prediction was comparable to ADC threshold-based delineation on the successfully treated cohort and superior to the Tmax threshold-based delineation in the unsuccessfully treated cohort. Conclusions: The confirmation of established predictors for stroke outcome (e.g., corticospinal tract integrity and total lesion volume) gives support to the proposed methodology-relating acute lesion loads to 3 month outcome assessments by way of correlation. Furthermore, the preliminary results indicate an association of further brain regions and structures with three month NIHSS outcome assessments. Hence, prediction models might observe an increased accuracy when incorporating regional (instead of global) lesion loads. Also, the results lend support to the clinical utilization of the automatically predicted volumes from FASTER, rather than the simpler DWI and PWI lesion delineations.

The effect of a single dose of escitalopram on sensorimotor networks.

INTRODUCTION: Serving as a pilot study of poststroke pharmacotherapy, the present investigation was intended to establish the effect of a single dose of escitalopram on motor task performance in normal volunteers. METHODS: Ten healthy volunteers of median age 63 years including four females performed a well-studied tactile manipulation task in two fMRI sessions using a double-blind cross-over design. The sessions began approximately three hours after ingestion of 20 mg escitalopram or placebo presented in pseudorandom order. The fMRI image sequences were submitted to principal component analysis (PCA). RESULTS: Based on volume correlations of task-related principal components with the mean component images derived in our previous study, we established the reproducibility of two networks of sensorimotor activity proposed there. The network reflecting motor control (cerebral pattern I) appeared invariably in placebo and verum conditions. In contrast, the other network, attributed to diminished motor control due to distracting mental processing (cerebral pattern II), emerged less regularly and exhibited more variability. Second-level PCAs of both conditions confirmed the findings of the initial analysis. Specifically, it validated the dominant and invariable expression of cerebral pattern I after application of a single dose of escitalopram. Dynamic causal modeling confirmed enhanced motor output as a result of a significantly increased connectivity between primary motor cortex and dorsal premotor cortex. CONCLUSION: This pilot study suggests the promise of stimulation by a specific serotonin reuptake inhibitor in regard to recovery and preservation of motor control after stroke.

Diverging lesion and connectivity patterns influence early and late swallowing recovery after hemispheric stroke.

Knowledge about the recovery of oral intake after hemispheric stroke is important to guide therapeutic decisions, including the administration of enteral tube feeding and the choice of the appropriate feeding route. They aimed to determine the localization and connectivity of lesions in impaired recovery versus recovered swallowing after initially dysphagic stroke. Sixty-two acute ischemic hemispheric stroke patients with impaired oral intake were included in a prospective observational cohort study. Voxel-based lesion-symptom mapping and probabilistic tractography were used to determine the association of lesion location and connectivity with impaired recovery of oral intake ≥7 days (indication for early tube feeding) and ≥4 weeks (indication for percutaneous endoscopic gastrostomy feeding) after stroke. Two distinct patterns influencing recovery of swallowing were recognized. Firstly, impaired recovery of oral intake after ≥7 days was significantly associated with lesions of the superior corona radiata (65% of statistical map, P < 0.05). The affected fibers were connected with the thalamus, primary motor, and supplemental motor areas and the basal ganglia. Secondly, impaired recovery of oral intake after ≥4 weeks significantly correlated with lesions of the anterior insula (54% of statistical map, P < 0.05), which was connected to adjacent operculo-insular areas of deglutition. These findings indicate that early swallowing recovery is influenced by white matter lesions disrupting thalamic and corticobulbar projection fibers. Late recovery is determined by specific cortical lesions affecting association fibers. This knowledge may help clinicians to identify patients at risk of prolonged swallowing problems that would benefit from enteral tube feeding. Hum Brain Mapp 38:2165-2176, 2017. © 2017 Wiley Periodicals, Inc.

Supplementary Motor Complex and Disturbed Motor Control - a Retrospective Clinical and Lesion Analysis of Patients after Anterior Cerebral Artery Stroke.

BACKGROUND: Both the supplementary motor complex (SMC), consisting of the supplementary motor area (SMA) proper, the pre-SMA, and the supplementary eye field, and the rostral cingulate cortex are supplied by the anterior cerebral artery (ACA) and are involved in higher motor control. The Bereitschaftspotential (BP) originates from the SMC and reflects cognitive preparation processes before volitional movements. ACA strokes may lead to impaired motor control in the absence of limb weakness and evoke an alien hand syndrome (AHS) in its extreme form. AIM: To characterize the clinical spectrum of disturbed motor control after ACA strokes, including signs attributable to AHS and to identify the underlying neuroanatomical correlates. METHODS: A clinical assessment focusing on signs of disturbed motor control including intermanual conflict (i.e., bilateral hand movements directed at opposite purposes), lack of self-initiated movements, exaggerated grasping, motor perseverations, mirror movements, and gait apraxia was performed. Symptoms were grouped into (A) AHS-specific and (B) non-AHS-specific signs of upper limbs, and (C) gait apraxia. Lesion summation mapping was applied to the patients' MRI or CT scans to reveal associated lesion patterns. The BP was recorded in two patients. RESULTS: Ten patients with ACA strokes (nine unilateral, one bilateral; mean age: 74.2 years; median NIH-SS at admission: 13.0) were included in this case series. In the acute stage, all cases had marked difficulties to perform volitional hand movements, while movements in response to external stimuli were preserved. In the chronic stage (median follow-up: 83.5 days) initiation of voluntary movements improved, although all patients showed persistent signs of disturbed motor control. Impaired motor control is predominantly associated with damaged voxels within the SMC and the anterior and medial cingulate cortex, while lesions within the pre-SMA are specifically related to AHS. No BP was detected over the damaged hemisphere. CONCLUSION: ACA strokes involving the premotor cortices, particularly the pre-SMA, are associated with AHS-specific signs. In the acute phase, motor behavior is characterized by the inability to carry out self-initiated movements. Motor control deficits may persist to a variable degree beyond the acute phase. Alterations of the BP point to an underlying SMC dysfunction in AHS.

A Thalamic-Fronto-Parietal Structural Covariance Network Emerging in the Course of Recovery from Hand Paresis after Ischemic Stroke.

AIM: To describe structural covariance networks of gray matter volume (GMV) change in 28 patients with first-ever stroke to the primary sensorimotor cortices, and to investigate their relationship to hand function recovery and local GMV change. METHODS: Tensor-based morphometry maps derived from high-resolution structural images were subject to principal component analyses to identify the networks. We calculated correlations between network expression and local GMV change, sensorimotor hand function and lesion volume. To verify which of the structural covariance networks of GMV change have a significant relationship to hand function, we performed an additional multivariate regression approach. RESULTS: Expression of the second network, explaining 9.1% of variance, correlated with GMV increase in the medio-dorsal (md) thalamus and hand motor skill. Patients with positive expression coefficients were distinguished by significantly higher GMV increase of this structure during stroke recovery. Significant nodes of this network were located in md thalamus, dorsolateral prefrontal cortex, and higher order sensorimotor cortices. Parameter of hand function had a unique relationship to the network and depended on an interaction between network expression and lesion volume. Inversely, network expression is limited in patients with large lesion volumes. CONCLUSION: Chronic phase of sensorimotor cortical stroke has been characterized by a large scale co-varying structural network in the ipsilesional hemisphere associated specifically with sensorimotor hand skill. Its expression is related to GMV increase of md thalamus, one constituent of the network, and correlated with the cortico-striato-thalamic loop involved in control of motor execution and higher order sensorimotor cortices. A close relation between expression of this network with degree of recovery might indicate reduced compensatory resources in the impaired subgroup.

Neural networks engaged in tactile object manipulation: patterns of expression among healthy individuals.

BACKGROUND: Somatosensory object discrimination has been shown to involve widespread cortical and subcortical structures in both cerebral hemispheres. In this study we aimed to identify the networks involved in tactile object manipulation by principal component analysis (PCA) of individual subjects. We expected to find more than one network. METHODS: Seven healthy right-handed male volunteers (aged 22 to 44 yrs) manipulated with their right hand aluminium spheres during 5 s with a repetition frequency of 0.5-0.7 Hz. The correlation coefficients between the principal component temporal expression coefficients and the hemodynamic response modelled by SPM (ecc) determined the task-related components. To establish reproducibility within subjects and similarity of functional connectivity patterns among subjects, regional correlation coefficients (rcc) were computed between task-related component image volumes. By hierarchically categorizing, selecting and averaging the task-related component image volumes across subjects according to the rccs, mean component images (MCIs) were derived describing neural networks associated with tactile object manipulation. RESULTS: Two independent mean component images emerged. Each included the primary sensorimotor cortex contralateral to the manipulating hand. The region extended to the premotor cortex in MCI 1, whereas it was restricted to the hand area of the primary sensorimotor cortex in MCI 2. MCI 1 showed bilateral involvement of the paralimbic anterior cingulate cortex (ACC), whereas MCI 2 implicated the midline thalamic nuclei and two areas of the rostral dorsal pons. CONCLUSIONS: Two distinct networks participate in tactile object manipulation as revealed by the intra- and interindividual comparison of individual scans. Both were employed by most subjects, suggesting that both are involved in normal somatosensory object discrimination.

Functional connectivity in tactile object discrimination: a principal component analysis of an event related fMRI-Study.

BACKGROUND: Tactile object discrimination is an essential human skill that relies on functional connectivity between the neural substrates of motor, somatosensory and supramodal areas. From a theoretical point of view, such distributed networks elude categorical analysis because subtraction methods are univariate. Thus, the aim of this study was to identify the neural networks involved in somatosensory object discrimination using a voxel-based principal component analysis (PCA) of event-related functional magnetic resonance images. METHODOLOGY/PRINCIPAL FINDINGS: Seven healthy, right-handed subjects aged between 22 and 44 years were required to discriminate with their dominant hand the length differences between otherwise identical parallelepipeds in a two-alternative forced-choice paradigm. Of the 34 principal components retained for analysis according to the 'bootstrapped' Kaiser-Guttman criterion, t-tests applied to the subject-condition expression coefficients showed significant mean differences between the object presentation and inter-stimulus phases in PC 1, 3, 26 and 32. Specifically, PC 1 reflected object exploration or manipulation, PC 3 somatosensory and short-term memory processes. PC 26 evinced the perception that certain parallelepipeds could not be distinguished, while PC 32 emerged in those choices when they could be. Among the cerebral regions evident in the PCs are the left posterior parietal lobe and premotor cortex in PC 1, the left superior parietal lobule (SPL) and the right cuneus in PC 3, the medial frontal and orbitofrontal cortex bilaterally in PC 26, and the right intraparietal sulcus, anterior SPL and dorsolateral prefrontal cortex in PC 32. CONCLUSIONS/SIGNIFICANCE: The analysis provides evidence for the concerted action of large-scale cortico-subcortical networks mediating tactile object discrimination. Parallel to activity in nodes processing object-related impulses we found activity in key cerebral regions responsible for subjective assessment and validation.

Brain areas involved in medial temporal lobe seizures: a principal component analysis of ictal SPECT data.

The study describes brain areas involved in medial temporal lobe (mTL) seizures of 12 patients. All patients showed so-called oro-alimentary behavior within the first 20 s of clinical seizure manifestation characteristic of mTL seizures. Single photon emission computed tomography (SPECT) images of regional cerebral blood flow (rCBF) were acquired from the patients in ictal and interictal phases and from normal volunteers. Image analysis employed categorical comparisons with statistical parametric mapping and principal component analysis (PCA) to assess functional connectivity. PCA supplemented the findings of the categorical analysis by decomposing the covariance matrix containing images of patients and healthy subjects into distinct component images of independent variance, including areas not identified by the categorical analysis. Two principal components (PCs) discriminated the subject groups: patients with right or left mTL seizures and normal volunteers, indicating distinct neuronal networks implicated by the seizure. Both PCs were correlated with seizure duration, one positively and the other negatively, confirming their physiological significance. The independence of the two PCs yielded a clear clustering of subject groups. The local pattern within the temporal lobe describes critical relay nodes which are the counterpart of oro-alimentary behavior: (1) right mesial temporal zone and ipsilateral anterior insula in right mTL seizures, and (2) temporal poles on both sides that are densely interconnected by the anterior commissure. Regions remote from the temporal lobe may be related to seizure propagation and include positively and negatively loaded areas. These patterns, the covarying areas of the temporal pole and occipito-basal visual association cortices, for example, are related to known anatomic paths.